Mucus barrier, mucins and gut microbiota: the expected slimy partners?

Gut, Journal Year: 2020, Volume and Issue: 69(12), P. 2232 - 2243

Published: Sept. 11, 2020

The gastrointestinal tract is often considered as a key organ involved in the digestion of food and providing nutrients to body for proper maintenance. However, this system composed organs that are extremely complex. Among different parts, intestine viewed an incredible surface contact with environment colonised by hundreds trillions gut microbes. role barrier has been studied decades, but exact mechanisms protection various complementary. them, integrity mucus one first lines tract. In past, 'slimy' partner was mostly simple lubricant facilitating progression bolus stools gut. Since then, researchers have made important progress, currently, regulation gaining increasing attention from scientific community. factors influencing barrier, microbiome plays major driving changes. Additionally, our dietary habits (ie, high-fat diet, low-fibre/high-fibre additives, pre- probiotics) influence at levels. Given layer linked appearance diseases, knowledge highly warranted. Here, we debate aspects focusing on its chemical composition, synthesis degradation microbiota well some characteristics both physiological pathological situations.

Language: Английский

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Regulation of Intestinal Barrier Function by Microbial Metabolites

Cellular and Molecular Gastroenterology and Hepatology, Journal Year: 2021, Volume and Issue: 11(5), P. 1463 - 1482

Published: Jan. 1, 2021

The human gastrointestinal tract (GI) harbors a diverse population of microbial life that continually shapes host pathophysiological responses. Despite readily available abundant metagenomic data, the functional dynamics gut microbiota remain to be explored in various health and disease conditions. Microbiota generate variety metabolites from dietary products influence functions. Since are produced close proximity epithelium, presumably they have significant impact on barrier function immune goal this review is discuss recent advances regulation intestinal function. While mechanisms action these only beginning emerge, mainly point small group shared pathways control Amidst expanding technology broadening knowledge, exploitation beneficial their restore balance will likely prove an extremely useful remedial tool. SummaryGut proximal regulate numerous responsive activities. Current article highlights area as well potential translational applications regulating disorders. 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Fecal induces remission patients active ulcerative colitis randomized controlled trial.Gastroenterology. 149: 102-109.e6Abstract (706) Scholar,20Kim Gadani Abdul-Baki Mitre R. recurrent infection: retrospective single-center chart review.JGH Open. 2019; 3: 4-9Crossref (9) One major metabolism components generation physiology function.21Maurice C.F. Haiser Turnbaugh P.J. Xenobiotics gene expression microbiome.Cell. 152: 39-50Abstract (468) restoration separate cell functions.22Singh Chandrashekharappa Bodduluri Baby B.V. Hegde Kotla N.G. Hiwale A.A. Saiyed T. Patel Vijay-Kumar Langille M.G.I. Douglas G.M. Cheng Rouchka Waigel S.J. Dryden G.W. Alatassi H.G. Haribabu Vemula P.K. Jala V.R. Enhancement integrity metabolite Nrf2 pathway.Nat Commun. 10: 89Crossref (108) 23Ewaschuk J.B. Diaz Meddings Diederichs Dmytrash Backer Looijer-van Langen Madsen K.L. Secreted bioactive Bifidobacterium infantis enhance function.Am Physiol Gastrointest Liver 295: G1025-G1034Crossref (359) 24Anderson R.C. Cookson McNabb W.C. Park McCann Kelly W.J. Roy N.C. Lactobacillus plantarum MB452 enhances increasing levels genes involved formation.BMC Microbiol. 2010; 316Crossref (210) Detailed yet elucidated, but knowledge concerning system gradually. Exploiting tool against In review, we how reinforce via bi-directional interactions cells. Further, treatment strategies mitigate composed 3 main interlinked/interdependent layers physical bacterial intrusion lumen. These include mucus layer, layer formed continuous sheet cells, third, forms system. acts immunological defense viruses, environmental toxins. selectively permeable allow for essential nutrients, electrolytes, amino acids, short-chain acids (SCFAs), sugars, water, select lumen into circulation. single interspersed functionally specialized differentiated enterocytes, Paneth goblet tuft enteroendocrine microfold which together form polarized monolayer separation lamina propria (Table 1). Among these, present intestine, whereas intestine colon, reviewed previously.25Peterson L.W. Artis cells: regulators homeostasis.Nat Rev 141-153Crossref (1145) 26Okumura Takeda Roles maintenance homeostasis.Exp 49: e338Crossref 27Allaire J.M. Crowley Law H.T. Chang S.-Y. Ko H.-J. Vallance epithelium: central coordinator immunity.Trends 39: 677-696Abstract (159) layer28Corfield interaction human.Microorganisms. 6: 78Crossref Scholar,29Corfield Carroll Myerscough Probert C.S. Mucins Biosci. 2001; D1321-D1357Crossref different types distinct roles maintaining homeostasis.Table 1Cell Types Barrier Their FunctionCell typesRole functionEnterocytes (small colon)•Responsible junctional complexes.•Nutrient absorption metabolization.•Balance shedding.•Secretion antimicrobial agents.•Changes expression/localization proteins permeability.Paneth intestine)•Source AMPs.•Directly sense critical homeostasis.•Paneth triggers inflammation dysfunction.•Lack leads necrotizing enterocolitis mice.Goblet intestine)•Produce release MUCs, forming glycoprotein barrier.•Lack MUC2 or O-glycan N-glycosylation susceptibility colitis.Tuft colon)•Secrete IL-25 IL-13 type 2 innate lymphoid (ILC2) promote hyperplasia mucin production.•Detect helminth infection expulse.Enteroendocrine colon)•Secret hormones GLP-2.•GLP-2 TJ ZO-1 occludin attenuates TNF-α–induced changes colon cells.•GLP-2 wound healing TGF-β–dependent manner.M intestine)•Antigen uptake.•M damage, during chronic elevates uptake microorganisms amplifying condition dysfunction.AMP, peptide; GLP-2, glucagon-like peptide-2; M cell, cell; MUC, mucin; TGF-β, transforming growth factor beta; TJ, junction; TNF-α, tumor necrosis alpha. Open table new tab AMP, (IECs) selective penetration electrolytes while simultaneously excluding pathogen-associated pattern, toxins, foreign antigens.30Kunzelmann Mall Electrolyte transport mammalian colon: implications disease.Physiol Rev. 2002; 82: 245-289Crossref Enterocytes connect each adhesive make up (TJ) proteins, adherens (AJ) gap desmosomes 2).31Niessen C.M. Tight junctions/adherens junctions: basic structure function.J Invest Dermatol. 127: 2525-2532Abstract (410) Scholar,32Groschwitz K.R. Hogan S.P. function: pathogenesis.J Allergy Clin 2009; 124 (quiz 21–22): 3-20Abstract (766) complexes not mechanically secure extracellular interactions, intracellular adaptor protein–mediated within Epithelial tightly paracellular (space cells) transcellular (through cell) posttranslational modifications proteins.33Van Itallie Anderson Claudins transport.Annu 2006; 68: 403-429Crossref (837) 34Fung K.Y.Y. Fairn G.D. W.L. Transcellular vesicular endothelial challenges opportunities.Traffic. 19: 5-18Crossref (47) 35Shigetomi Ikenouchi Regulation post-translational membrane proteins.J Biochem. 163: 265-272Crossref (0) located apical side belt-like ring at lateral membrane. consist 50 crucial cell-to-cell adhesion health.36Chiba Osanai Murata Kojima Sawada Transmembrane junctions.Biochim Biophys Acta. 1778: 588-600Crossref (276) Some tetraspan single-span transmembrane link cytoskeletal proteins.37Schulzke J.D. Fromm meets function.Ann N Y Sci. 1165: 1-6Crossref (1) (OCLN), claudin (CLDN), tricellulin molecules proteins.38Furuse Hirase Itoh Nagafuchi Yonemura Tsukita Occludin: integral localizing junctions.J Cell Biol. 1993; 123: 1777-1788Crossref (1975) 39Furuse Fujita Hiiragi Fujimoto Claudin-1 -2: junctions no sequence similarity occludin.J 1998; 141: 1539-1550Crossref (1554) 40Ikenouchi Furuse Sasaki Tricellulin constitutes tricellular contacts cells.J 171: 939-945Crossref (535) 41Garrido-Urbani Bradfield P.F. Imhof dynamics: (JAMs).Cell Tissue Res. 355: 701-715Crossref (64) Other zonula occludens (ZO) (ZO-1, ZO-2, ZO-3) scaffold proteins. postsynaptic density protein-95/Drosophila disc large suppressor/ZO-1 (PDZ) binding domains plaque (eg, F-actin) complex.42Odenwald M.A. Choi Kuo W.T. Singh Sailer Fanning A.S. Turner scaffolding coordinates actomyosin specializations vivo.J Biol Chem. 293: 17317-17335Abstract (20) seals generally when anastomose adjacent based size/charge space. Adherence primarily contribute mechanical structures, properties, extensively elsewhere.43Garcia-Hernandez Quiros Nusrat claudins: homeostasis inflammation.Ann 1397: 66-79Crossref (104) 44Laukoetter Bruewer complex.Curr Opin 22: 85-89Crossref (173) 45Buckley disease.Cold Spring Harb Perspect A02931Crossref (110) 46Farkas A.E. Pharmacological targeting inflamed barrier.Curr Pharm Des. 5400-5414Crossref (3) 47Choi Yeruva Contributions barriers disease.Exp 358: 71-77Crossref (29) 48Zuo targets effectors homeostasis.Cell 2020; 327-340Abstract ScholarTable 2Structural Components Cells FunctionStructural componentsJunctional proteinsExamples dysfunctionTight proteinsZO, occludin, claudins, tricellulin, JAM•IFN-γ TNF-α mediated organization ZO-1, claudin-1, claudin-4, occluding, JAM-A downregulate function.•Downregulation claudin-3, claudin-5, claudin-8 claudin-2 MLCK phosphorylation function.Adherens proteinsCadherins, catenins•Downregulated E-cadherin–catenin complex mediates impairment barrier.DesmosomeDesmoglein, desmocollins•Desmoglein (Dsg2) deficiency loss integrity.Gap junctionsConnexin•Connexin-43 plays intercellular communication vesicles, tunneling nanotubes junctions.IFN-γ, interferon gamma; JAM, molecules; MLCK, myosin light-chain kinase; alpha; ZO, occludens. IFN-γ, disruption AJ, causing dysregulated translocation/transportation mediators, potentially manifests inflammation. Increased further perpetuates permeability. following sections describe altered state Defective combination dysregulation tract–related limited drug-induced toxicity, cancer. occurs apoptosis/enterocyte death, degradation, due TJs. independently regulated consequences other. section describes responsible dysfunction. As described previous sections, was solutes water cross TJs size charge selectivity: pore pathway48Zuo 49Turner disease.Nat 799-809Crossref (1727) 50Anderson Van Physiology junction.Cold 1: a002584Crossref (563) leak pathway.48Zuo Scholar,51Buschmann M.M. Rajapakse Raleigh D.R. Lingaraju Zha Abbott McAuley Breskin L.A. Wu Weber C.R. Occludin OCEL-domain required macromolecular flux.Mol 24: 3056-3068Crossref (94) pathway exclusively excludes diameter ≤8 Å high-conductance route. CLDN-2 CLDNs 10a, 10b, 15, 16, 17 were pathway. contrast pathway, allows macromolecule flux exclusion limit ∼100 lower conductance.51Buschmann believed (MLCK), where constitutively sufficient increase pathway–dependent vivo.52Shen Black E.D. Witkowski Lencer W.I. Guerriero Schneeberger E.E. Myosin light chain regulates remodeling structure.J 119: 2095-2106Crossref (308) Scholar,53Su Clayburgh Nalle S.C. Sullivan E.A. Abraham Targeted causes activation contributes development experimental colitis.Gastroenterology. 136: 551-563Abstract (273) OCLN, pathway.54Yu McCarthy K.M. Francis S.A. McCormack Lai Rogers Lynch R.D. Knockdown phenotypic alterations cells.Am 288: C1231-C1241Crossref (239) discussions published.48Zuo Scholar,49Turner 9

Language: Английский

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Hallmarks of Health

Cell, Journal Year: 2020, Volume and Issue: 184(1), P. 33 - 63

Published: Dec. 18, 2020

Language: Английский

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Microplastics detected in cirrhotic liver tissue

EBioMedicine, Journal Year: 2022, Volume and Issue: 82, P. 104147 - 104147

Published: July 11, 2022

The contamination of ecosystem compartments by microplastics (MPs) is an ubiquitous problem. MPs have been observed in mice tissues, and recently human blood, stool placenta. However, two aspects remain unclear: whether accumulate peripheral organs, specifically the liver, if liver cirrhosis favours this process. We aimed to examine tissue samples determine liver.This proof-of-concept case series, conducted Germany, Europe, analyzed 6 patients with 5 individuals without underlying disease. A total 17 (11 3 kidney spleen samples) were according final protocol. reliable method for detection MP particles from 4 30 µm was developed. Chemical digestion samples, staining Nile red, subsequent fluorescent microscopy Raman spectroscopy performed. Morphology, size composition polymers assessed.Considering limit detection, all disease tested negative MPs. In contrast, concentrations cirrhotic tissues positive showed significantly higher compared Six different microplastic ranging detected.This series assessed presence found six cirrhosis, but not those Future studies are needed evaluate hepatic accumulation represents a potential cause pathogenesis fibrosis, or consequence portal hypertension.No funding received conducting investigator driven study.

Language: Английский

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Effect of gut microbiota on LPS-induced acute lung injury by regulating the TLR4/NF-kB signaling pathway

International Immunopharmacology, Journal Year: 2020, Volume and Issue: 91, P. 107272 - 107272

Published: Dec. 22, 2020

Language: Английский

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Paracellular permeability and tight junction regulation in gut health and disease

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2023, Volume and Issue: 20(7), P. 417 - 432

Published: April 25, 2023

Language: Английский

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Gut barrier disruption and chronic disease

Trends in Endocrinology and Metabolism, Journal Year: 2022, Volume and Issue: 33(4), P. 247 - 265

Published: Feb. 9, 2022

Language: Английский

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Underestimated health risks: polystyrene micro- and nanoplastics jointly induce intestinal barrier dysfunction by ROS-mediated epithelial cell apoptosis

Particle and Fibre Toxicology, Journal Year: 2021, Volume and Issue: 18(1)

Published: June 7, 2021

Micro- and nanoplastic pollution has become a global environmental problem. Nanoplastics in the environment are still hard to detect because of analysis technology limitations. It is believed that when microplastics found environment, more undetected nanoplastics around. The current "microplastic exposure" fact mixture micro- exposures. Therefore, biological interaction between organisms among different sizes should not be neglected.We measured biodistribution three polystyrene (PS) particles (50 nm PS, PS50; 500 PS500; 5000 PS5000) under single co-exposure conditions mice. We explored underlying mechanisms by investigating effects on major components intestinal barrier (the mucus layer, tight junctions epithelial cells) four intestine segments (duodenum, jejunum, ileum colon) amounts both PS500 PS5000 increased they were co-exposed with PS50 for 24 h These due primarily permeability mouse intestines. also confirmed there was combined toxicity This manifested as causing severe dysfunction than caused or alone. PS reactive oxygen species (ROS)-mediated cell apoptosis findings further an oxidants antioxidants pretreatment study. In addition, mice after 28-day repeated dose exposure.There intestines, which ROS-mediated Considering most recent studies have been conducted using particle size, health risks exposure may underestimated.

Language: Английский

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Inflammatory and Microbiota-Related Regulation of the Intestinal Epithelial Barrier

Frontiers in Nutrition, Journal Year: 2021, Volume and Issue: 8

Published: Sept. 13, 2021

The intestinal epithelial barrier (IEB) is one of the largest interfaces between environment and internal milieu body. It essential to limit passage harmful antigens microorganisms and, on other side, assure absorption nutrients water. maintenance this delicate equilibrium tightly regulated as it for human homeostasis. Luminal solutes ions can pass across IEB via two main routes: transcellular pathway or paracellular pathway. Tight junctions (TJs) are a multi-protein complex responsible regulation permeability. TJs control through have key role in maintaining integrity. Several factors, including cytokines, gut microbiota, dietary components known regulate TJs. Gut microbiota participates several functions modulation cells immune system release metabolites, such short-chain fatty acids (SCFAs). Mediators released by induce cell damage dysfunction. subsequent disruption allows into mucosa leading further inflammation. Growing evidence indicates that dysbiosis, activation, dysfunction diseases, irritable bowel syndrome (IBS), inflammatory disease (IBD), gluten-related conditions. Here we summarize interplay mucosal their involvement IBS, IBD, disorders.

Language: Английский

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Functions of Gut Microbiota Metabolites, Current Status and Future Perspectives

Aging and Disease, Journal Year: 2022, Volume and Issue: 13(4), P. 1106 - 1106

Published: Jan. 1, 2022

Gut microbiota, a collection of microorganisms that live within gastrointestinal tract, provides crucial signaling metabolites for the physiological hosts. In healthy state, gut microbiota are helpful maintaining basic functions hosts, whereas disturbed production these can lead to numerous diseases such as metabolic diseases, cardiovascular neurodegenerative and cancer. Although there many reviews about specific mechanisms on is no comprehensive summarization metabolites. this Opinion, we discuss knowledge including types their ways acting targets. addition, summarize pathologic in health shaping composition nutrition. This paper be understanding roles thus provide guidance developing suitable therapeutic strategies combat microbial-driven improve health.

Language: Английский

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